tbuckley/cabot-search huggingface dataset:
Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study
Authors: Marcela Prada, Fabian Eichelmann, Clemens Wittenbecher, Olga Kuxhaus, Matthias B. Schulze
Journal: Diabetes Care (2023)

OBJECTIVE Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class–specific PUFA concentrations with type 2 diabetes risk. RESEARCH DESIGN AND METHODS In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. RESULTS Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23–1.26) and monoacylglycerols (HR 0.59; 0.38–0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23–2.14), phosphatidylethanolamines (HR 1.87; 1.32–2.65), and phosphatidylinositol (HR 1.40; 1.05–1.87); free fatty acids (HR 1.44; 1.10–1.90); and cholesteryl esters (HR 1.47; 1.09–1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. CONCLUSIONS Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.
Glomerular Hyperfiltration Predicts Kidney Function Decline and Mortality in Type 1 and Type 2 Diabetes: A 21-Year Longitudinal Study
Authors: Diego Moriconi, Luca Sacchetta, Martina Chiriacò, Lorenzo Nesti, Giovanna Forotti, Andrea Natali, Anna Solini, Domenico Tricò
Journal: Diabetes Care (2023)

OBJECTIVE To evaluate the prognostic value of glomerular hyperfiltration on long-term kidney-related outcomes and mortality in patients with diabetes. RESEARCH DESIGN AND METHODS We retrospectively analyzed 21-year longitudinal data from 314 patients with long-standing type 1 or type 2 diabetes. Glomerular hyperfiltration was identified based on the age- and sex-specific distribution of measured glomerular filtration rate (mGFR) by 99mTc-DTPA dynamic renal scintigraphy. The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease (ESKD), or cardiorenal death. The kidney-specific outcome was a composite of doubling of serum creatinine, ESKD, or renal death. RESULTS Over a median of 21.0 years, the primary composite outcome occurred in 25 (39.7%), 24 (38.1%), and 46 (24.5%) participants with high mGFR (H-mGFR) (n = 63), low mGFR (L-mGFR) (n = 63), or normal mGFR (N-mGFR) (n = 188), respectively. Compared with N-mGFR, the hazard ratio (HR) for the primary composite outcome was 2.09 (95% CI 1.25–3.49) in H-mGFR and 1.81 (1.05–3.16) in L-mGFR. The HR for the kidney-specific composite outcome was 4.95 (2.21–11.09) in H-mGFR and 3.81 (1.70–8.56) in L-mGFR. The HRs for doubling of serum creatinine and cardiorenal death were 4.86 (2.18–10.90) and 2.18 (1.24–3.83) in H-mGFR and 4.04 (1.77–9.20) and 2.26 (1.27–4.01) in L-mGFR, respectively. CONCLUSIONS Glomerular hyperfiltration, similar to hypofiltration, increases the combined risk of worsening kidney function and mortality from cardiovascular or renal causes in patients with diabetes. These findings encourage the active screening of these patients to optimize risk stratification and treatment of subclinical kidney disease.
Association and Interaction of Genetics and Area-Level Socioeconomic Factors on the Prevalence of Type 2 Diabetes and Obesity
Authors: Sara J. Cromer, Chirag M. Lakhani, Josep M. Mercader, Timothy D. Majarian, Philip Schroeder, Joanne B. Cole, Jose C. Florez, Chirag J. Patel, Alisa K. Manning, Sherri-Ann M. Burnett-Bowie, Jordi Merino, Miriam S. Udler
Journal: Diabetes Care (2023)

OBJECTIVE Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity. RESEARCH DESIGN AND METHODS Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T2D and BMI and 2) area-level socioeconomic risk (educational attainment) measures. The primary analysis included 26,737 participants of European genetic ancestry in MGBB with replication in UKB (N = 223,843), as well as in participants of non-European ancestry (MGBB N = 3,468; UKB N = 7,459). RESULTS The area-level socioeconomic measure most strongly associated with both T2D and obesity was percent without a college degree, and associations with disease prevalence were independent of genetic risk (P &amp;lt; 0.001 for each). Moving from lowest to highest quintiles of combined genetic and socioeconomic burden more than tripled T2D (3.1% to 22.2%) and obesity (20.9% to 69.0%) prevalence. Favorable socioeconomic risk was associated with lower disease prevalence, even in those with highest genetic risk (T2D 13.0% vs. 22.2%, obesity 53.6% vs. 69.0% in lowest vs. highest socioeconomic risk quintiles). Additive effects of genetic and socioeconomic factors accounted for 13.2% and 16.7% of T2D and obesity prevalence, respectively, explained by these models. Findings were replicated in independent European and non-European ancestral populations. CONCLUSIONS Genetic and socioeconomic factors significantly interact to increase risk of T2D and obesity. Favorable area-level socioeconomic status was associated with an almost 50% lower T2D prevalence in those with high genetic risk.
Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes
Authors: Yang Hu, Gang Liu, Edward Yu, Biqi Wang, Clemens Wittenbecher, JoAnn E. Manson, Eric B. Rimm, Liming Liang, Kathryn Rexrode, Walter C. Willett, Frank B. Hu, Qi Sun
Journal: Diabetes Care (2023)

OBJECTIVE The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Among participants with incident diabetes identified in the Nurses’ Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy (ULCDS) LCDS were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality. RESULTS Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. CONCLUSIONS Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality.
Effects of Intensive Systolic Blood Pressure Lowering on End-Stage Kidney Disease and Kidney Function Decline in Adults With Type 2 Diabetes Mellitus and Cardiovascular Risk Factors: A Post Hoc Analysis of ACCORD-BP and SPRINT
Authors: Yahya M.K. Tawfik, Benjamin W. Van Tassell, Dave L. Dixon, William L. Baker, John Fanikos, Leo F. Buckley
Journal: Diabetes Care (2023)

OBJECTIVE To determine the effects of intensive systolic blood pressure (SBP) lowering on the risk of major adverse kidney outcomes in people with type 2 diabetes mellitus (T2DM) and/or prediabetes and cardiovascular risk factors. RESEARCH DESIGN AND METHODS This post hoc ACCORD-BP subgroup analysis included participants in the standard glucose-lowering arm with cardiovascular risk factors required for SPRINT eligibility. Cox proportional hazards regression models compared the hazard for the composite of dialysis, kidney transplant, sustained estimated glomerular filtration rate (eGFR) &amp;lt;15 mL/min/1.73 m2, serum creatinine &amp;gt;3.3 mg/dL, or a sustained eGFR decline ≥57% between the intensive (&amp;lt;120 mmHg) and standard (&amp;lt;140 mmHg) SBP-lowering arms. RESULTS The study cohort included 1,966 SPRINT-eligible ACCORD-BP participants (40% women) with a mean age of 63 years. The mean SBP achieved after randomization was 120 ± 14 and 134 ± 15 mmHg in the intensive and standard arms, respectively. The kidney composite outcome occurred at a rate of 9.5 and 7.2 events per 1,000 person-years in the intensive and standard BP arms (hazard ratio [HR] 1.35 [95% CI 0.85–2.14]; P = 0.20). Intensive SBP lowering did not affect the risk of moderately (HR 0.96 [95% CI 0.76–1.20]) or severely (HR 0.92 [95% CI 0.66–1.28]) increased albuminuria. Including SPRINT participants with prediabetes in the cohort did not change the overall results. CONCLUSIONS This post hoc subgroup analysis suggests that intensive SBP lowering does not increase the risk of major adverse kidney events in individuals with T2DM and cardiovascular risk factors.
Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Matthew J Ehrhardt, Jan M Leerink, Renée L Mulder, Annelies Mavinkurve-Groothuis, Wouter Kok, Anju Nohria, Paul C Nathan, Remy Merkx, Esmée de Baat, Ogechukwu A Asogwa, Roderick Skinner, Hamish Wallace, E A M Lieke Feijen, Maëlle de Ville de Goyet, Maya Prasad, Edit Bárdi, Vesna Pavasovic, Helena van der Pal, Brice Fresneau, Charlotte Demoor-Goldschmidt, Ulrike Hennewig, Julia Steinberger, Chris Plummer, Ming Hui Chen, Arco J Teske, Nadia Haddy, Elvira C van Dalen, Louis S Constine, Eric J Chow, Gill Levitt, Melissa M Hudson, Leontien C M Kremer, Saro H Armenian
Journal: The Lancet Oncology (2023)
Safety and Efficacy of the Omnipod 5 Automated Insulin Delivery System in Adults With Type 2 Diabetes: From Injections to Hybrid Closed-Loop Therapy
Authors: Georgia M. Davis, Anne L. Peters, Bruce W. Bode, Anders L. Carlson, Bonnie Dumais, Todd E. Vienneau, Lauren M. Huyett, Trang T. Ly
Journal: Diabetes Care (2023)

Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial.Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmol/mol). Participants completed 2 weeks of CGM sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mg/dL and <54 mg/dL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mg/dL).Participants (N = 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmol/mol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mg/dL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mg/dL remained low during both ST and AID (median [interquartile range] 0.0% [0.00%, 0.06%] vs. 0.00% [0.00%, 0.03%]; P = 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmol/mol; P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID.Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population.
Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study
Authors: Joan Valls, Armando Baena, Gino Venegas, Marcela Celis, Mauricio González, Carlos Sosa, Jorge Luis Santin, Marina Ortega, Ana Soilán, Elmer Turcios, Jacqueline Figueroa, Margarita Rodríguez de la Peña, Alicia Figueredo, Andrea Verónica Beracochea, Natalia Pérez, Josefina Martínez-Better, Oscar Lora, Julio Yamil Jiménez, Diana Giménez, Laura Fleider, Yuly Salgado, Sandra Martínez, Yenny Bellido-Fuentes, Bettsy Flores, Silvio Tatti, Verónica Villagra, Aurelio Cruz-Valdez, Carolina Terán, Gloria Inés Sánchez, Guillermo Rodríguez, Maria Alejandra Picconi, Annabelle Ferrera, Laura Mendoza, Alejandro Calderón, Raul Murillo, Carolina Wiesner, Nathalie Broutet, Silvana Luciani, Carlos Pérez, Teresa M Darragh, José Jerónimo, Rolando Herrero, Maribel Almonte
Journal: The Lancet Global Health (2023)
Impact of malnutrition on early outcomes after cancer surgery: an international, multicentre, prospective cohort study
Authors: Aya Riad, Stephen R Knight, Dhruv Ghosh, Pamela A Kingsley, Marie Carmela Lapitan, Marie Dione Parreno-Sacdalan, Sudha Sundar, Ahmad Uzair Qureshi, Apple P Valparaiso, Riinu Pius, Catherine A Shaw, Thomas M Drake, Lisa Norman, Adesoji O Ademuyiwa, Adewale O Adisa, Maria Lorena Aguilera, Sara W Al-Saqqa, Ibrahim Al-Slaibi, Aneel Bhangu, Bruce M Biccard, Peter Brocklehurst, Sorrel Burden, Kathryn Chu, Ainhoa Costas-Chavarri, Anna J Dare, Muhammed Elhadi, Cameron J Fairfield, J Edward Fitzgerald, James Glasbey, Mark I. van Berge Henegouwen, J.C. Allen Ingabire, T Peter Kingham, Ismaïl Lawani, Bettina Lieske, Richard Lilford, Laura Magill, Mayaba Maimbo, Janet Martin, Sonia Mathai, Kenneth A McLean, Rachel Moore, Dion Morton, Dmitri Nepogodiev, John Norrie, Faustin Ntirenganya, Francesco Pata, Thomas Pinkney, Rajkumar Kottayasamy Seenivasagam, Antonio Ramos-De la Medina, Tracey E Roberts, Hosni Khairy Salem, Joana Simões, Richard JE Skipworth, Richard T Spence, Neil Smart, Stephen Tabiri, Evropi Theodoratou, Hannah Thomas, Thomas G Weiser, Malcolm West, John Whitaker, Edwin Yenli, Ewen M Harrison
Journal: The Lancet Global Health (2023)
Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study
Authors: Kerstin D Rosenberger, Lam Phung Khanh, Frank Tobian, Ngoun Chanpheaktra, Varun Kumar, Lucy Chai See Lum, Jameela Sathar, Ernesto Pleités Sandoval, Gabriela M Marón, Ida Safitri Laksono, Yodi Mahendradhata, Malabika Sarker, Ridwanur Rahman, Andrea Caprara, Bruno Souza Benevides, Ernesto T A Marques, Tereza Magalhaes, Patrícia Brasil, Guilherme Amaral Calvet, Adriana Tami, Sarah E Bethencourt, Tam Dong Thi Hoai, Kieu Nguyen Tan Thanh, Ngoc Tran Van, Nam Nguyen Tran, Viet Do Chau, Sophie Yacoub, Kinh Nguyen Van, María G Guzmán, Pedro A Martinez, Quyen Nguyen Than Ha, Cameron P Simmons, Bridget A Wills, Ronald B Geskus, Thomas Jaenisch, Zabir Hasan, Kilma Wanderley Lopes Gomes, Lyvia Patricia Soares Mesquita, Cynthia Braga, Priscila M.S. Castanha, Marli T. Cordeiro, Luana Damasceno, Bophal Chuop, Sonyrath Ouk, Reaksmey Sin, Sopheary Sun, Mayling Alvarez Vera, Guillermo Barahona, Bladimir Cruz, Dorothea Beck, Roger Gaczkowski, Thomas Junghanss, Ivonne Morales, Marius Wirths, Santha Kumari Natkunam, Bee Kiau Ho, Sazaly AbuBakar, Juraina Abd-Jamil, Sharifah Faridah Syed Omar, Erley F. Lizarazo, María F. Vincenti-González, Erley F. Lizarazo, Robert Tovar, María F. Vincenti-González, Tam Cao Thi, Hong Dinh Thi Tri, Huy Huynh Le Anh, Duyen Huynh Thi Le, Thanh Lai Thi Cong, Van Nguyen Thi Hong, Linh Nguyen Thi My, Thuy Tran Thi Nhu, Thuy Truong Thi Thu, Nuoi Banh Thi, Trinh Huynh Lam Thuy, Hiep Nguyen Thi Thu, Van Tran Thi Kim, Luan Vo Thanh, Bich Dang Thi, Huong Dinh Thi Thu, Huy Dinh Van, Huyen Nguyen Nguyen, Huong Vu Thi Thu
Journal: The Lancet Global Health (2023)
Profile of emergency department overuse in hospitalized patients with pulmonary disease and its impact on mortality
Authors: J. Barbosa, D. Organista, T. Rodrigues, A.F. Matos, A. Barardo, A. Escoval, C. Bárbara, F. Rodrigues
Journal: Pulmonology (2023)

Portugal is one of the countries with the highest number of visits to the emergency department (ED), 31% classified as "non-urgent" or "avoidable." The objectives of our study were to evaluate the size and characteristics of patients with pulmonary disease who overuse the ED, and identify factors associated with mortality. A retrospective cohort study was conducted, based on the medical records of ED frequent users (ED-FU) with pulmonary disease who attended a university hospital center in the northern inner city of Lisbon from January 1 to December 31, 2019. To evaluate mortality, a follow-up until December 31, 2020 was performed. Over 5,567 (4.3%) patients were identified as ED-FU and 174 (0.14%) had pulmonary disease as the main clinical condition, accounting for 1,030 ED visits. 77.2% of ED visits were categorized as "urgent/very urgent." A high mean age (67.8 years), male gender, social and economic vulnerability, high burden of chronic disease and comorbidities, with a high degree of dependency, characterized the profile of these patients. A high proportion (33.9%) of patients did not have a family physician assigned and this was the most important factor associated with mortality (p<0.001; OR: 24.394; CI 95%: 6.777–87.805). Advanced cancer disease and autonomy deficit were other clinical factors that most determined the prognosis. Pulmonary ED-FU are a small group of ED-FU who constitute an aged and heterogeneous group with a high burden of chronic disease and disability. The lack of an assigned family physician was the most important factor associated with mortality, as well as advanced cancer disease and autonomy deficit.
Alpha1-antitrypsin deficiency in Greece: Focus on rare variants
Authors: S.A. Papiris, M. Veith, A.I. Papaioannou, V. Apollonatou, I. Ferrarotti, S. Ottaviani, A. Tzouvelekis, V. Tzilas, N. Rovina, G. Stratakos, I. Gerogianni, Z. Daniil, L. Kolilekas, K. Dimakou, G. Pitsidianakis, N. Tzanakis, S. Tryfon, F. Fragopoulos, E.M. Antonogiannaki, A. Lazaratou, E. Fouka, D. Papakosta, P. Emmanouil, N. Anagnostopoulos, T. Karampitsakos, K. Vlami, M. Kallieri, P. Lyberopoulos, S. Loukides, D. Bouros, A. Bush, M. Balduyck, C. Lombard, V. Cottin, J.F. Mornex, C.F. Vogelmeier, T. Greulich, E.D. Manali
Journal: Pulmonology (2023)

A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. to investigate genotype and clinical profile of Greeks with AATD. Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.
Proinsulin–to–C-Peptide Ratio as a Marker of β-Cell Function in African American and European American Adults
Authors: Catharine A. Couch, Francesca Piccinini, Lauren A. Fowler, W. Timothy Garvey, Barbara A. Gower
Journal: Diabetes Care (2023)

OBJECTIVE The primary purpose of the current study was to test the hypothesis that the proinsulin–to–C-peptide (PI-to-CP) ratio, as an index of proinsulin secretion, would be higher and associated with indices of β-cell function in African American adults relative to European American adults without type 2 diabetes. RESEARCH DESIGN AND METHODS Participants were 114 African American and European American adult men and women. A 2-h oral glucose tolerance test was conducted to measure glucose, insulin, C-peptide, and proinsulin and derive indices of β-cell response to glucose. The Matsuda index was calculated as a measure of insulin sensitivity. The disposition index (DI), the product of insulin sensitivity and β-cell response, was calculated for each phase of β-cell responsivity. Pearson correlations were used to investigate the relationship of the PI-to-CP ratio with each phase of β-cell response (basal, Φb; dynamic, Φd; static, Φs; total, Φtot), disposition indices (DId, DIs, DItot), and insulin sensitivity. Multiple linear regression analysis was used to evaluate independent contributions of race, BMI, and glucose tolerance status on PI-to-CP levels before and after adjustment for insulin sensitivity. RESULTS African American participants had higher fasting and 2-h PI-to-CP ratios. The fasting PI-to-CP ratio was positively associated with Φb, and the fasting PI-to-CP ratio and 2-h PI-to-CP ratio were inversely associated with DId and insulin sensitivity only in African American participants. CONCLUSIONS The PI-to-CP ratio could be useful in identifying African American individuals at highest risk for β-cell dysfunction and ultimately type 2 diabetes.